Making connections

Abstract

Deleting a gene called Sema5A, which has been linked to autism in humans, causes neurons to form more connections in mice, and also alters how these mutant mice interact with other mice.

Keywords: 3D electron microscopy; dentate granule cells; hippocampus; mouse; neuroscience; plexin; semaphorin; synaptogenesis.

Figure 1.. Deleting the gene for Semaphorin 5A in mice increases the density of synapses and changes how mutant mice interact with other mice.

Duan, Wang et al. report that semaphorin 5A (blue) inhibits the formation of synapses (shown inside the grey oval; left) in granule cells in the dentate gyrus of the hippocampus by interacting with a protein called plexin-A2 (green). This occurs in granule cells that developed in the embryo and have matured, and also in granule cells that formed during adulthood. In the absence of Semaphorin 5A, the density of synapses increases (right). Wild-type mice (bottom left) prefer to interact with an unfamiliar mouse (light brown) over a familiar mouse (dark brown). In contrast, Sema5A knockout mice (bottom right) show greater preference for a familiar mouse, which mimics the social anxiety seen in autism spectrum disorders.